Skull-Mounted Drug and Pressure Sensor

ABSTRACT

A skull-mounted drug and pressure sensor (SOS), a smart pump (ISP) electrically coupled to the SOS and a drug delivery and communications catheter communicating the SOS with the ISP are combined for a first embodiment. A skull-mounted (SOS), a metronomic biofeedback pump (MBP) electrically coupled to the SOS and a drug delivery and communications catheter having a sending and receiving optical fiber communicating the SOS with the MBP are combined for a second embodiment. A third embodiment combines a (SOS), an implantable power and communication unit (PCU) electrically coupled to the SOS, and a drug delivery and communications catheter for communicating the SOS with the PCU and for communicating the exterior source of the drug to the SOS. A fourth embodiment combines a ventricular catheter with a CSF accessible chamber and drug delivery port; and an implantable stand-alone skull-mounted drug and pressure sensor (SPS).

RELATED APPLICATIONS

The present application is a divisional of U.S. patent application Ser.No. 15/594,251, filed on May 12, 2017, which in turn is related to U.S.Provisional Patent Application, Ser. No. 62/336,446, filed on May 13,2016, which are each incorporated herein by reference and to whichpriority is claimed pursuant to 35 USC 119.

BACKGROUND Field of the Technology

The invention relates to the field of implantable pumps used in thetreatment of brain cancers and neurological disease. It also relates toa skull-mounted drug and pressure sensor (SOS) that has a built-inoptical sensor to detect drugs in a chamber built into a catheter thatextends from a skull-mounted body of the SOS into the brain.

Description of the Prior Art

An Ommaya reservoir is an intraventricular catheter system that wasoriginally invented in 1963 by Ayub K. Ommaya, a Pakistani neurosurgeonand that can be used for the aspiration of cerebrospinal fluid or forthe delivery of drugs (e.g. chemotherapy) into the cerebrospinal fluid.It consists of a catheter disposed in one lateral brain ventricleattached to a reservoir implanted under the scalp. It is used to treatbrain tumors, leukemia/lymphoma or leptomeningeal disease by intrathecaldrug administration. In the palliative care of terminal cancer, anOmmaya reservoir can be inserted for intraventricular injection ofmorphine.

Development of the Ommaya reservoir was a significant breakthrough intreatment of brain cancer and neurological disease when it wasintroduced, as it provided a minimally invasive method for neurosurgeonsto bypass the blood brain barrier and deliver drug directly to thebrain. However, the major risks associated with the use of the Ommayareservoir involves infections and complications due to malposition ormalfunction of the device. In addition, there can be blockage or leakageof the catheter, which can lead to improper drug delivery anddevelopment of lesions along the catheter. The use of Ommaya to deliverchemotherapy drugs by a bolus injection into the brain usually leads totoxic levels of the chemotherapy drug immediately following delivery, ashort interval of drug concentration within the therapeutic rangefollowed by long periods of sub-therapeutic drug concentration whichcould accelerate the development of drug resistance. It is well knownthat chemotherapy into the brain also can lead to elevated brain CSFpressure and hydrocephalus if not addressed. These problems with use ofthe Ommaya reservoir for drug delivery are addressed by the inventionsdescribed herein.

BRIEF SUMMARY

A first embodiment of the illustrated embodiments is directed to askull-mounted drug and pressure sensor (SOS) electrically connected to apump. The SOS has a wired connection to a pump (called implanted smartpump (ISP) in this application) and a drug delivery tube contained inmulti-lumen tubing or catheter communicating the SOS with the ISP. Thecatheter includes a dual lumen tube. The wired connection enables theSOS to be smaller as the ISP has the battery and most, but not all, ofthe electronics for the SOS is located inside the ISP.

A second embodiment includes an SOS optical sensor (no pressure sensor)connected by optical fibers to the pump. The optical sensor is locatedinside the metronomic biofeedback pump (MBP) pump casing and the SOSonly has the optics to receive the light signal from the pump, send itthrough the sensing chamber containing the cerebro-spinal fluid (CSF)and return the signal to the pump (called a metronomic biofeedback pump(MBP) in this application) where it will be analyzed. For additionalclarity, the MBP has the LEDs, photodiode, the electronic analysishardware and software within the pump case whereas the ISP does not. Inthe first embodiment the LEDs, the photodiodes and electronic analysishardware are in the SOS and not contained within the ISP. The SOScontains the necessary optics to bend the light and connect it to thepump. The MBP contains the LED's light source connected to the fiberoptic cables and the receiving photo diode to convert the returninglight that has passed through the CSF into an electrical signal thatwill be analyzed by the electronics included in the MBP. The MBP and theSOS are connected by a tri-lumen tube—one is a drug delivery tube andtwo fiber optic tubes for sending and receiving light. In thisembodiment, the pressure sensor is in the pump. The connector betweenthe MBP and the SOS is tri-laminar tubing. One lumen is for drugdelivery to the SOS drug delivery port, and two lumens are for the fiberoptic cables; one for sending light from the MBP to the CSF opticalchamber and one is for the return light from the chamber back to the MBPto a photodiode and the electronics for calculating the drugconcentrations and other necessary data management actions.

A third embodiment is a stand-alone system that includes the optical andpressure sensor (SOS) as described in the first embodiment connected toa power and communication unit (PCU). The PCU is not connected to a pumpbut communicates wirelessly to an external receiver or mobile systemmonitor, optionally to a pump and to a clinician programmer. In thisembodiment, the SOS is totally “independent” of the pump. The SOS isconnected to the power communications unit (PCU) which has a ventricularaccess port for optional drug delivery to the brain or sampling CSF. ThePCU has the battery, and wireless low power Bluetooth electronics forcommunicating with the outside world. It also has, optionally,additional computational electronics for managing data and data storage.The SOS has the optical sending and receiving and electronics necessaryto measure the drug in CSF and communicate that information to the PCU.The information is sent optionally directly to the pump andnon-optionally to a mobile system monitor and the clinician programmer.These external devices can optionally communicate with any internalpumps or other implanted devices, but there is no drug delivery catheteror other connection with another device or ability to “close the loop”.

A fourth embodiment is directed to a stand-alone skull-mounted pressuresensor (SPS) with a ventricular access port for measuring CSF pressureand drug delivery and providing for electronic communication with theclinical programmer and mobile system monitor. This skull-mountedpressure sensor (SPS) with ventricular access is a less complex SOS.This SPS differs from the SOS in that the separate optical sensorcomponents are removed and it contains a battery, appropriateelectronics and a low power Bluetooth communication system tocommunicate measured brain CSF pressure to an external device. Theventricular access port (VAP) then can be used to relieve the CSFover-pressure by withdrawing CSF fluid. It can also deliver drugsthrough the VAP to the brain via the fluid pathway on the ventricularcatheter. The SPS has a catheter stem (ventricular catheter) that isplaced into the ventricle to measure CSF pressure and has fluidiccommunication with the VAP chamber and from the VAP chamber to thepressure sensor. It is also optionally fitted in subembodiments with acatheter fitted with a valve assembly to deliver CSF fluid to theperitoneal cavity in cases of significant brain over pressure such as inhydrocephalus.

The SOS provides the ability to measure the concentration of a drug inthe cerebro-spinal fluid (CSF) at the site of delivery and communicatethe data to an external device or to the pump. This significantenhancement over existing Ommaya reservoir technology allows thephysician to monitor drug diffusion away from the delivery site, therebyverifying CSF patency and proper placement of the ventricularly placedsensor and drug delivery catheter. The SOS also does not have areservoir for holding CSF fluid or provide access to CSF fluid via aport as an Ommaya port does unless it is the third embodiment above thatis connected to the PCU or the SPS in the fourth embodiment above.

The systems are implanted in between the scalp and the skull with thecatheter inserted into the ventricles of the brain. The skull mountedembodiments have a low enough profile not to erupt through the skin whenplaced on the skull and below the skin or to be uncomfortable (forexample: to lay one's head on a pillow) or cause significant skinerosion. In some embodiments where the vertical height is too large (>3mm) a bone “bed” is carved into the skull of sufficient depth to countersink the device not to exceed the 3 mm vertical height limit beyond thesurface of the skull bone. In some cases, the vertical height limits canbe exceeded where the skin is loose and there in less likelihood oferuption through the skin. In addition, and optionally, as part of thedeployment of the device, when the height of the device is too high insome embodiments to be acceptable by carving a depression in the skullbone, a hole can be drilled through the skull to enable the profile belowered sufficiently so the device will not erupt through the skin.

In third embodiment above a septum on the PCU provides the doctor apoint for direct delivery of drug and collection of CSF samples. Thefirst and second embodiments above do not have a septum for collectingCSF fluid because the pump is used to provide the drug and there is acatheter access port in the pumping system which allows for thecollection of CSF as desired. The SOS implantation protocols are basedon existing surgical procedures for Ommaya implantation and forelectrical stimulation devices such as Parkinson's disease stimulatorsthat suppress tremor. Once implanted, the SOS can be used as astandalone device to deliver drug via pumps in the first and secondembodiments above only or via the injection port in the third and fourthembodiments above only and measure drug concentration at the site ofdelivery, or paired with an implantable drug delivery pump connected tothe proximal end of the delivery catheter. The distal end of the SOScatheter is implanted into the ventricle.

During operation, the device can be run in several modes for datamanagement: 1) concentration data can be delivered immediately aftermeasurement and drug delivery protocols may optionally be altereddepending on the information, or 2) it can be set to record a series ofmeasurements over several time points and then after a delay towirelessly or by wired connection to the ISP transfer the data where itcan be further processed. In all cases the information will becommunicated to the clinician programmer, the patient management deviceand to a cloud electronic medical record (EMR) storage site.

All these SOS embodiments optionally have two or more suture anchors(eyelets or “ears” not illustrated) in the device casing or on thebiocompatible coating, if present, to act as locations where thesurgeons can suture the device to the skull or suitable tissue andligaments to prevent movement.

While the apparatus and method has or will be described for the sake ofgrammatical fluidity with functional explanations, it is to be expresslyunderstood that the claims, unless expressly formulated under 35 USC112, are not to be construed as necessarily limited in any way by theconstruction of “means” or “steps” limitations, but are to be accordedthe full scope of the meaning and equivalents of the definition providedby the claims under the judicial doctrine of equivalents, and in thecase where the claims are expressly formulated under 35 USC 112 are tobe accorded full statutory equivalents under 35 USC 112. The disclosurecan be better visualized by turning now to the following drawingswherein like elements are referenced by like numerals.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an exploded perspective view of the SOS and ISP of the firstembodiment.

FIG. 2 is an enlarged upper perspective view of the SOS of FIG. 1.

FIG. 3 is an upper perspective view of the SOS of FIG. 2 with the top ofthe casing removed to expose the pressure sensor and electronicsdisposed therein.

FIG. 4 is an upper perspective view of the SOS of FIG. 3 with the LEDchip shown in exploded view to illustrate the fiber optic ports locatedbelow the LED chip.

FIG. 5 is a lower perspective view of the SOS of FIG. 4 with the LEDchip shown in exploded view.

FIG. 6a is a side cross sectional view of the assembled SOS of FIGS. 1-5as seen through section lines 6B-6B of FIG. 6 b.

FIG. 6b is a top plan view of the SOS of FIG. 1 with the top of thecasing in place illustrating section lines 6B-6B.

FIG. 7a is a side cross sectional view of the assembled SOS of FIGS. 1-5as seen through section lines 7A-7A if FIG. 7b , which are perpendicularto section lines 6B-6B of FIG. 6 b.

FIG. 7b is a top plan view of the SOS of FIG. 1 with the top of thecasing in place illustrating section lines 7A-7A.

FIG. 8 is a diagram of the main functional elements in the SOS and ISPof FIGS. 1-7.

FIG. 9 is a diagram of the main functional elements in the secondembodiment of the SOS and MBP.

FIG. 10 is an exploded perspective view of the SOS and MBP of the secondembodiment.

FIG. 11 is an exploded perspective view of the SOS and PCU of the thirdembodiment.

FIG. 12 is an enlarged perspective view of the PCU of FIG. 11 shownconnected to its multilumen tubing and electrical connector.

FIG. 13 is an enlarged perspective view of the PCU of FIG. 12 shown withthe top cover removed to illustrate the battery, electronics andventricular access port included therein.

FIG. 14 is a diagram of the main functional elements in the thirdembodiment of the SOS and PCU of FIGS. 11-13.

FIG. 15 is a perspective view of the stand-alone skull-mounted pressuresensor (SPS) with a ventricular access port of the forth embodiment.

FIG. 16 is a perspective view of the stand-alone skull-mounted pressuresensor (SPS) of FIG. 15 with the top cover removed to show the pressuresensor, ventricular access port (VAP), battery and electronics therein.

FIG. 17a is a side cross sectional view of the stand-alone skull-mountedpressure sensor (SPS) of FIG. 15 as seen through section lines 17C-17Cof FIG. 17 b.

FIG. 17b is a top plan view of stand-alone skull-mounted pressure sensor(SPS) of FIG. 15 with the top of the casing in place illustrated sectionlines 17C-17C.

FIG. 18 is a perspective view of a sub-embodiment of fourth embodimentwith the top cover removed that enables the optional drainage of CSFthrough a magnetically adjustable valve (a leak) to relieve high CSFpressure and reduce the potential of developing hydrocephalus.

FIG. 19 is a perspective view of the sub-embodiment of FIG. 18 connectedto a magnetic valve and peritoneal catheter tip.

The disclosure and its various embodiments can now be better understoodby turning to the following detailed description of the preferredembodiments which are presented as illustrated examples of theembodiments defined in the claims. It is expressly understood that theembodiments as defined by the claims may be broader than the illustratedembodiments described below.

DETAILED DESCRIPTION OF THE PREFERRED FOUR EMBODIMENTS

FIG. 1 illustrates perspective view of the ISP 1, the SOS 3, aventricular catheter 10 for insertion into the brain and a dual lumendrug supply catheter 2 which connects the pump 1 to the SOS 3. The duallumen catheter includes one lumen 4 for drug delivery and a second lumen5 for the wires necessary for bidirectional communication between theSOS 3 and the pump 1. The drug delivery catheter lumen 4 connects to theSOS through port 7 and the electronics wires 5 connect via pass throughport 6 as illustrated in FIG. 2. A drug or multiple drugs will beprovided through catheter lumen 4 coming from an implantable pump 1 oran external pump (not shown) through a pump reservoir (not shown), orthrough the ventricular access port 30 in the fourth embodiment in FIGS.15-16, and thence via ventricular catheter 10 into the ventricleemanating from the drug delivery port 8. The CSF/drug sensing chamber 21shown in FIG. 6 is in fluid communication with the CSF via holes 9 inFIG. 2. These holes 9 allow drug containing CSF to enter the chamber 21and be analyzed by the optical sensor as described below.

FIG. 3 is a cut away perspective drawing of the SOS 3 with the top coverremoved showing the pressure sensor 12 which measures CSF pressure andalso confirms that there is no leak's or obstruction in the catheter orleakage in key connections. The electronics board 11's and the opticalsensor 13's location and LED breadboard 14 for the SOS are alsoillustrated in FIGS. 3 and 4. FIG. 4 provides a less obstructed view ofthe optical sensor where the LED breadboard 14 has been removed to showthe LED origination fiber 16 and the reflected light returning opticalfiber 15. A perspective bottom view of the LED breadboard 14 is shown inFIG. 5 illustrating the source for the LED sending unit 17 andphotodiode receiving unit 18. FIG. 5 also illustrates the silicone skullseat 19 which provides a biocompatible coating to the bottom of the SOSand a strain relief seat 20 which provides extra support for theventricular catheter 10 extending from the SOS.

FIG. 6a is a perpendicular side cross sectional view taken throughsection lines 6B-6B of FIG. 6b showing a more detailed view of thedevice and especially illustrating the fiber optic pathway. The sourceLED 16 is attached to the proximal end of the sending fiber optic fiber39 which goes through to the lens 41 which then transmits the lightthrough the sensing chamber 21 to the distal reflective mirror 42. Thelight beam then transverses the sensing chamber 21 again essentiallydoubling the path length of the sensing distance to the lens 41 and thenback up through the receiving fiber optic 40 to the receiving photodiode15. The bullet tip 43 covers the end of the sensing chamber 21 and thereflective mirror 42 and allows for a minimally destructive penetrationof brain tissue on insertion of the ventricular catheter 10. The sensingchamber 21 has holes 9 cut through its walls to allow for free diffusionof CSF fluid containing drug into and out of the sensing chamber 21. Theelectronics board and components 11 are placed at the bottom of thehermetically sealed SOS device and leave room for the pressure sensor 12which is in fluid communication with the ventricular catheter 10 and thesensing chamber 21.

FIG. 7a is a perpendicular side cross sectional view as seen throughsection lines 7A-7A of FIG. 7b to illustrate a more detailed crosssection of the SOS and ventricular catheter 10 highlighting thedrug-delivery pathway through the SOS and the ventricular catheter 10and the pressure sensor 12 in fluidic communication with the ventricularcatheter 10. The drug delivered from the ISP 1 through the catheter 2enters the SOS 3 through the fluid access port 7 via catheter tube 4 andthrough internal tubing 22, through the drug-delivery connector 23 downthe ventricular catheter 10 to the drug delivery port 8. Thedrug-delivery channel is separated from the sensing chamber 21 to enabledrug mixing in the ventricle before it diffuses into the sensing chamber21 for drug optical sensing (light absorption by drug in the CSF) andthe concentration calculation by the electronics 11 (in SOS and ISP).

FIG. 8 is a block diagram of the power, communication and fluid systemsfor the ISP 1, catheter system and the SOS in the first embodiment. TheISP 1 and SOS 3 illustrated here have distinct functions. The SOS 3 isdesigned to provide the essential functions for optical sensing andcapturing the sensed information. It also houses the drug-deliverychannel 22. The ISP 1 is the source of the drug, the wirelesscommunication system, the drug pump, the power, the main computing andanalysis electronics and the software. The diagram labels the maincomponents of the ISP 1, the catheter 2, ventricular catheter 10 and theSOS 3. The wired connector in catheter 2 is connected to the electricalconnector tips 4 in FIG. 1 on each end the fluid path in catheter 2illustrated with a white line. The clear line is the drug delivery lumen4 which is connected to the ISP and through connector 7 to the SOS 3.The dotted lines around the ISP 1 and SOS 3 illustrate the perimeter ofeach device. ISP 1 includes a battery 54 coupled to the electricalcomponents within ISP 1 and to the SOS 3 via the catheter 2. Power andanalog circuitry 50 is coupled to battery 54 to supply the varioussystems of ISP 1 and SOS 3 with appropriately conditioned power andcontrol signals consistent with conventional design principles.Microcontroller 68 turns on and off the SOS electronics to makemeasurements, interprets the measurements, converts them into physicalunits and communicates this information to the ISP 1. All thedrug-delivery controls, data logs, alarms and utilization of data isdone by the ISP electronics. A microcontroller and Bluetooth low energy(BLE) radio 52 coupled to antenna 31 provides bidirectional control,data and communication signals to and from ISP 1 and SOS 3 and otheroutputs from the SOS 3 and the power and analog circuitry. The Bluetoothcommunication 52 will also be in contact with the physician programmerand the mobile system monitor (not illustrated) to enable externalmonitoring of the pump and SOS function and health. Drugs are storedwithin reservoir 60 which is coupled to and monitored by pressure sensorand valve 62. The pressure sensor 62 is located at the refill inlet andcan detect if the reservoir 60 is over pressured on filling thereservoir 60. The pressure sensor 62 is also used to monitor volume inthe reservoir 60 and calculate the amount of drug being delivered and ifthe delivery is accurate during the refill procedures. Pump 56 iscommunicated to reservoir 60 and has an output pressure sensor 58 formonitoring the pressure supplied to catheter 2. Outlet pressure sensor58 will be used to determine if there is a clog in the catheter andcorrect delivery volume or pressure changes. Drugs are delivered fromcatheter 2 to SOS pressure and temperature sensor 64, through which thedrugs are delivered to catheter 10. Sensor 64 is used in conjunctionwith pressure sensor 58 to determine if there is an occlusion in thepump catheter or the ventricular catheter 10. Both pressure sensors 58and 64 together will be used to determine if there is a leak in the pumpcatheter. Pressure sensor 64 will also be used to measure intercranialpressure (ICP) and trip an alarm to tell the physician if it exceeds apressure level set by the physician. Brain over-pressure can be adangerous situation and lead to hydrocephalus. LED bundle 70 andphotodetector 72 are coupled to sending optical fiber 39 and receivingoptical fiber 40 respectively. LED bundle 70 is powered and controlledby control and analog circuit 66. Photodetector 72 provides an outputsignal to control and analog circuit 66, which digitizes it and providesit to microcontroller 68. Communication and data signals arebidirectionally supplied to communication line 76 and provided from andto microcontroller and the Bluetooth communication chip and BLE radio 52via the catheter wires in catheter lumen 5.

FIG. 9 is a block diagram of the fiber optic pathways, communication andfluid systems for the MBP 24, tri-lumen catheter system 25 and theskull-mounted ventricular catheter fixture 26 in the second embodimentabove. The diagram labels the main components of the MBP 24, thecatheter 25 and the ventricular catheter fixture 26. The MBP 24 andventricular catheter fixture 26 illustrated here have distinctfunctions. The ventricular catheter fixture 26 is a minimal housing toprovide the optical fibers 27 and 28 a conduit from the optical sensor78 in the MBP 24 through catheter 2 to the sensing chamber 21 and tohouse the drug delivery catheter 22 to port 8 in the ventricle. The MBP24 is the source of the drug, the wireless communication system 52, thedrug pump 56, the battery power source 52, the optical sensor 18 and LEDbundle 17 the main computing and analysis electronics 50 and thesoftware. The advantage of the second embodiment is that the size of theventricular catheter fixture 26 is significantly reduced. The MBP 24 isnecessarily more complex and larger but there will be sufficient roomfor this change in size at the implantation site. For clarity, the fluidpath 4 is connected to the MBP 24 and fixture 26 via the fluid connector7 in the white line. The fiber optic cables (bolded, dark black lines)for fiber optic sending lead 28 and the fiber optic cable for receivinglead 27 is connected to the ports (unlabeled) on the MBP 24 and fixture26 respectively. In the second embodiment, the fixture 26 does notcollect the data from the optical sensor but rather sends it backdirectly to the MBP 24 which contains the optical sensor circuitry 78and the necessary electronics to calculate the drug concentration andprocess, store and communicate the data. In addition, the pressuresensor system 62, 58 is housed within the MBP 24 and not in the fixture26 where the fluid path is short. This enables the ventricular fixture26 to be quite simple and physically small as it will not contain anyelectronics, the LEDs, or photo diode. In the second embodiment, thefixture 26 is simply a conduit for the drug-delivery catheter 25 and theoptical fibers 27, 28 and a fixture to hold them in the proper placewith respect to ventricular catheter 10. The main sensing and datamanagement and calculation duties are entirely conducted within the MBP24.

FIG. 10 is a perspective view of MBP 24, catheter assembly 25 and theskull-mounted ventricular catheter fixture 26. The catheter assembly 25is a tri-lumen tube containing the drug delivery lumen 4, and thesending fiber optic 28 and the receiving fiber optic 27.

FIG. 11 is a perspective view for third embodiment above which is a“stand-alone” system that consist of SOS 3 and the dual lumen catheter 2connected to a power and communication unit (PCU) 29 which enables theSOS 3 to operate without connection to the ISP 1. The PCU will enablethe SOS sensor to be independent by providing power, electronics andcommunication capabilities. Optionally the SOS 3 could also be used asan independent sensor and work through external communication with otherproperly designed drug-delivery systems. In the third embodiment, thePCU 29 provides the power, electronic data collection, management,calculations and wireless communication that will enable externalcommunications with the clinician programmer, patient mobile systemmonitor (not shown), cloud-based EMR storage database and optionally theISP 1 to close a data feedback loop based on the drug and pressureinformation received from the SOS 3. FIG. 11 shows the PCU 29 contains aself-healing septum covering the ventricular access port 30 thatcommunicates through drug delivery lumen 4 of catheter 2 to the SOS 3and delivers drug through the drug delivery port 8 using an externalsyringe or external pump connected through the skin and into theventricular access port 30. It should be pointed out another intendeduse of the ventricular access port 30 is to withdraw CSF fluid shouldthere be brain high pressure (potential hydrocephalus) or if the doctorwishes to analyze CSF directly from the patient. A wired connection fromthe SOS 3 goes through connector 6 to wire 5 to the PCU 29 and providesthe power needed to operate the SOS electronics, LEDs, photo diode andother necessary functions in the SOS 3 as well as the PCU 29 powerrequirements. The SOS 3 and catheter 2 in first and third embodimentsare the same. The differences between these two embodiments is that thepower and communications are done in the ISP 1 or PCU 29 respectively.

FIG. 12 is a perspective drawing showing the Bluetooth antenna 31 andthe antenna holder 32. FIG. 13 is a perspective drawing of the PCU 29with the top cover removed to provide more detail about the internalcomponents. The PCU 29 includes a battery 33, ventricular access port30, the Bluetooth communication chip 80 on the electronics board 11connected to the Bluetooth antenna holder 32 and the Bluetooth antenna31.

FIG. 14 is a block diagram of the power, communication and fluid systemsfor the PCU 29, catheter system 2 and the SOS 3 in third embodiment. Thediagram labels the main components of the PCU 29, the catheter 2 and theSOS 3. For clarity, the wired connector is in a black bold line incatheter 2 and is connected to the electrical connector tip 4 on eachend the fluid path is illustrated with a white line. The dotted linesaround the PCU 29 and SOS 3 illustrate the perimeter of each device. Asin the prior embodiments, PCU 29 includes a battery 54, power and analogcircuitry 50, microcontroller and BLE radios 52, and antenna 31. VAP 30is included in PCU 29 and the components of PCU 29 are communicated toSOS 3 through catheter 2. SOS 3 includes pressure sensor 58 communicatedto ventricular catheter 10. LED 70, photodiode 72, control and analogcircuitry 66 and microcontroller 68 as in the prior embodiments areincluded in SOS 3. The SOS 3 in first and third embodiments are thesame.

Under certain circumstances during chemotherapy brain pressure builds upand if left untreated can become a serious medical concern and if notreturned to normal will result in hydrocephalus. The fourth embodimentaddresses this using a smart device that measures brain pressure andtemperature and communicates it to a clinician programmer and a mobilesystem monitor. Medical personnel so informed can then take appropriateaction. The skull-mounted pressure sensor (SPS) 43 also contains aventricular access port 30 to enable the removal of CSF fluid, measuredrug in CSF or deliver drugs into the ventricle. FIG. 15 is aperspective drawing of the stand-alone skull-mounted pressure sensor(SPS) 43 of the fourth embodiment illustrating the VAP 30, theventricular catheter 34 that is in fluid communication with the CSFaccess ports 35, the pressure/temperature sensor 12 and the VAP 30 shownin FIG. 16. The fourth embodiment does not contain optical sensors asits primary function is to determine CSF pressure and temperature andnot to calculate drug concentration in CSF. It does contain the VAP 30to provide the medical personnel convenient options should brainpressure be found to be elevated.

FIG. 16 is a cut-away drawing of the SPS 43 with the top removed to showthe main components on the skull-mounted portion. The SPS 43 has abattery 33 to power the electronics board 11, a pressure sensor 12 influid communication with the VAP 30 and the ventricular catheter 34.FIG. 17a is a side cross sectional view of the SPS 43 as seen throughsection lines 17C-17C of FIG. 17b . FIG. 17a illustrates in more detailthe fluid pathway from the pressure sensor 12 through the VAP chamber 36to the ventricular catheter 34 via a fluid path 37 in VAP catheter 34,through VAP septum 39, VAP chamber 36, the CSF chamber 38, the CSFaccess ports 35. The CSF access port 35 enables fluid communicationbetween the CSF chamber 38 and the CSF in the ventricle.

The SPS 43 may optionally have a connector 39 a from the VAP 30 to theexterior of the SPS 43 which may be capped to prevent leakage from theVAP 30 as shown in FIG. 18. The connector 39 a is in fluid communicationwith the VAP 30, the pressure sensor 12 and the brain catheter 34. Thecap on the connector prevents leakage from the CSF until it is removed.The cap on the connector 39 a can be optionally removed and connected toa variety of catheter options depending on the medical indication.Optionally and most preferred when needed to reduce brain pressure,connector 39 a may be uncapped and connected to a catheter assembly 40that has sufficient length to drain into the peritoneal cavity as shownin FIG. 19. The catheter assembly 40 is optionally fitted with a valve41 that can be magnetically adjusted to enable a prescribed CSF leakrate to enable brain pressure reduction. Other kinds of valves can alsobe employed such as passive flap valves designed to leak at certainpressures and mechanical valves that can be adjusted through the skin.The tip of the catheter 42 is placed in the peritoneal cavity to enablethe leaked CSF to drain into the peritoneal cavity and relieve excessbrain pressure. In this configuration, the PSP 43 acts like ahydrocephalus shunt.

Measurement of drug concentration in a sample is based on therelationship described by the Beer-Lambert equation, which states thatthe attenuation of a light source when passed through a sample solutionis related to the concentration of material present in the solution. Inthe SOS 3 of the first embodiment FIGS. 1-8, multiple LED sources areused that emit at specific frequencies in the UV/VIS range. Thesefrequencies are chosen to maximize sensitivity, as drugs strongly absorbin the selected LED emission range. In total and for this example, thesystem contains four LED's of drug specific light frequencies. Thesystem could have fewer or more LEDs depending on the complexity of thedesired analysis. This gives the system flexibility to be modifiedaccording to the needs to measure a specific drug or a group of drugs ornatural components found in the CSF. This optical analysis system couldbe used in other locations in the body where there is an extracellularfluid for which the concentration of a fluid component (for example adrug, protein, hormone, etc.) is to be measured. This UV/VIS light istransmitted as shown in FIG. 6 via a fiber-optic 39 to the CSF chamber21 at the end of the brain catheter 10 segment. This chamber 21 includesa perforated wall 9 to allow CSF fluid to freely move in and out of thechamber 21, while preventing any brain tissues that could obstruct thelight path from entering.

From the end of the transmitting fiber-optic 39, the UV/VIS light willpass through a lens 41, pass through the CSF in chamber 21, be reflectedback from mirror 42 through the sensing chamber 21, through the lens 41and returned by fiber optic cable 40 to the receiving photo diode(sensor) 15. The mirror 42 is a double 90° reflection of a conicalmirror. The fiber optic cable 40 will carry the returned UV/VIS light toa UV/VIS light sensor 15. Here, the light intensity will be converted toan electrical signal proportional with the UV/VIS light intensity. Theanalog signal will then be amplified, filtered and converted to adigital format by the onboard electronics, generally denoted byreference numeral 11 best shown in FIG. 3.

In the first embodiment, the SOS only communicates through wires to theISP 1 via catheter 2 and the onboard electronics is to manage LEDs, thedata collection and storage from the sensor and a variety ofhousekeeping duties. FIG. 2 illustrates the SOS's connector fittings forthe catheter wires 6 and the drug delivery connector 7.

The embedded micro-controller and Bluetooth controller 52 in the thirdembodiment provide the bidirectional data communication, datameasurement schedule and data storage. The internal button lithiumbattery 54 provides the necessary operating power. To conserve energy,the electronics hardware 50, 52 will spend the majority of the time in“sleep mode”.

Since the absorption spectra of most drugs features at least oneprominent peak, the UV/VIS LEDs frequencies can be selected to coveroptionally one or more leading edges of selected peaks one or more majorpeak maxima, optionally one or more trailing peak edges and a neutralreference—where absorption does not change with drug concentration—overthe drug specific frequencies range.

The optical sensor has one or more LEDs depending on the requirements ofa predetermined analysis complexity. For more flexibility and forgeneral applications the number of LEDs can be increased to cover awider range of wavelengths and sensitivities. For the current devicesillustrated but not limited to these examples the optimum number of LEDswas settled on four to three for absorption measurement and one as acalibration and reference LED. The optical sensor can be customized tomeasure any optical absorption profile and for any wavelength for whichLEDs are available. This makes the optical sensor a remarkably flexible,implantable drug sensor with a very wide range of potential measurementapplications. When a measurement is made, each LED is turned onindividually (in sequence) one at a time and a measurement is made. Thepeak LED measurement will be used to calculate the absorption andconsequently the drug concentration. The leading and trailing LEDs willprovide the drug specificity measurement. The reference LED will measurethe baseline value, which is made possible by selecting a frequency thatis not absorbed by the drug and the selected fluid. Inside the LEDpackage 70 there is a photo-diode 72. This photo-sensor measures thepackage window reflected light which is used as the feedback signal toan optional constant light closed loop circuit included in electronics.This optional constant light regulation minimizes the LED chip amplitudedrift and allows for a relative fast measurement cycle. The LED lowpower and fast measurements eliminates any UV/VIS effect on the CSF orother fluid and increases the battery operating time.

The pressure sensor has three main uses. The pressure/temperature sensorin the first and second embodiments will optionally monitor the systemfor leaks in the drug delivery catheter, clogged catheter and CSFpressure and temperature. CSF pressure is sometimes elevated duringcancer chemotherapy to the brain and it is an important added feature toinform medical personnel when it is elevated. In the third embodimentwhere there is a PCU it will not be necessary to monitor for a leak andin this embodiment the pressure/temperature sensor will be absent. Inthe fourth embodiment, the PSP, the pressure/temperature sensor willmonitor CSF pressure only as there is no pumping drug delivery pathwayonly a ventricular access port for optional drug delivery or CSFsampling.

The SOS 3 can be used in the following cancer applications:

-   -   Intrathecal therapy where it's important to monitor the local        drug concentration at the site where the drug is delivered        (applies to all forms of cancer that have spread to the brain)        where CSF flow has been verified.    -   For use in the cavum septum pellucidum (CSP) because        measurements of the concentration of chemotherapeutic agent by        the SOS 3 can verify CSF patency (normal CSF flow) based on the        fact that drug concentrations would get to be too high.

Risks associated with current SOS reservoir design include:

-   -   The most common risks associated with the use of the SOS        reservoir primarily deal with complications due to malposition        or malfunction of the device. Either condition may result in        blockage or leakage of the catheter 10, leading to improper drug        delivery.    -   Lesions may develop along the catheter 10, infection may        develop, and chemotherapy may reach toxic levels.    -   In cancer patients scheduled for surgical intervention, who have        previously received chemotherapy via an Ommaya or SOS reservoir,        there is some evidence of increased perioperative (between        admission and discharge from hospital) morbidity due to a        diseased condition existing at the time of surgery with Ommaya        reservoirs.

There are several additional embodiments of this invention and theextensions of these modified embodiments. For example, the apparatuscould be made without a drug delivery cannula from the ISP 1 or catheter2 built into the SOS as described in the third embodiment. Then theoptical sensor would still operate but only measure internal CSF fluidsor drugs in CSF fluids administered separately through an externalcannula or via a systemic route that gets to the brain via thecirculation system. This embodiment would still have a cannula from thePCU's VAP 30 for adding drugs via an external pump or syringe from theVAP 30 or for withdrawing fluids from the CSF. The opportunities forutility go well beyond cancer as this could be delivering drugs ormonitoring drugs for Parkinson's Disease, epilepsy, bipolar disease,Alzheimer's Disease, schizophrenia and depression where patientcompliance is an issue and other CNS and neurodegenerative diseases.

The metronomic biofeedback pump 24 (MBP or ISP) is a fully implantablesmart infusion device (ISP 1 or implanted smart pump), designed tolocally deliver chemotherapies or medication over time to a target site.Then this would make the pump purely a single pump system.

Many alterations and modifications may be made by those having ordinaryskill in the art without departing from the spirit and scope of theembodiments. Therefore, it must be understood that the illustratedembodiment has been set forth only for the purposes of example and thatit should not be taken as limiting the embodiments as defined by thefollowing embodiments and its various embodiments.

In the illustrated embodiments only drug delivery into the brainventricle is disclosed. With a different catheter designs drugs could bedelivered into any tissue in the brain, elsewhere in the body or into asolid tumor where the optical chamber 21 would optionally be omitted.Delivery of drugs into any area of the brain is expressly contemplatedas within the scope of the invention, namely for various noncancerousdiseases such as Parkinson's Disease, depression, epilepsy,schizophrenia bipolar disease, neurodegenerative diseases by regular ormore importantly by convection enhanced delivery (CED). CED is atherapeutic strategy that was developed to facilitate targeted deliveryof pharmaceuticals to the brain. The CED procedure involves a minimallyinvasive surgical exposure of the brain, followed by placement of smalldiameter catheters directly into the brain tumor. Subsequently, infusionof therapeutics into the tumor occurs over several hours to saturate thetarget tissue. As this approach effectively bypasses theblood-brain-barrier, it allows for delivery of macromolecular drugs thatwould not normally enter the brain to effectively reach highconcentrations within brain tumor tissue. In order to reach similarconcentrations as those achieved with CED, systemically administeredconventional chemotherapeutic agents would need to be given at dosesthat would result in significant toxicity. Thus, an additional benefitof CED is that it simultaneously limits exposure of the remainder of thebody to the therapeutic agent and thus minimizes systemic drug-relatedadverse effects. CED is an important delivery method for brain andtissue delivery. In general for CED only the catheter tip disclosedabove would need to be changed.

Therefore, it must be understood that the illustrated embodiment hasbeen set forth only for the purposes of example and that it should notbe taken as limiting the embodiments as defined by the following claims.For example, notwithstanding the fact that the elements of a claim areset forth below in a certain combination, it must be expresslyunderstood that the embodiments includes other combinations of fewer,more or different elements, which are disclosed in above even when notinitially claimed in such combinations. A teaching that two elements arecombined in a claimed combination is further to be understood as alsoallowing for a claimed combination in which the two elements are notcombined with each other, but may be used alone or combined in othercombinations. The excision of any disclosed element of the embodimentsis explicitly contemplated as within the scope of the embodiments.

The words used in this specification to describe the various embodimentsare to be understood not only in the sense of their commonly definedmeanings, but to include by special definition in this specificationstructure, material or acts beyond the scope of the commonly definedmeanings. Thus, if an element can be understood in the context of thisspecification as including more than one meaning, then its use in aclaim must be understood as being generic to all possible meaningssupported by the specification and by the word itself.

The definitions of the words or elements of the following claims are,therefore, defined in this specification to include not only thecombination of elements which are literally set forth, but allequivalent structure, material or acts for performing substantially thesame function in substantially the same way to obtain substantially thesame result. In this sense it is therefore contemplated that anequivalent substitution of two or more elements may be made for any oneof the elements in the claims below or that a single element may besubstituted for two or more elements in a claim. Although elements maybe described above as acting in certain combinations and even initiallyclaimed as such, it is to be expressly understood that one or moreelements from a claimed combination can in some cases be excised fromthe combination and that the claimed combination may be directed to asub-combination or variation of a sub-combination.

Insubstantial changes from the claimed subject matter as viewed by aperson with ordinary skill in the art, now known or later devised, areexpressly contemplated as being equivalently within the scope of theclaims. Therefore, obvious substitutions now or later known to one withordinary skill in the art are defined to be within the scope of thedefined elements.

The claims are thus to be understood to include what is specificallyillustrated and described above, what is conceptionally equivalent, whatcan be obviously substituted and also what essentially incorporates theessential idea of the embodiments.

We claim:
 1. An apparatus comprising: an implantable skull-mounted drugand pressure sensor (SOS); a metronomic biofeedback pump (MBP)electrically coupled to the SOS; a drug delivery and communicationscatheter having a sending and receiving optical fiber communicating theSOS with the MBP, where the SOS includes an optical ventricular catheterwith a drug delivery port and a CSF accessible optical chambercommunicated with the sending and receiving optical fibers included inthe drug delivery and communications catheter, and where the MBPincludes a drug reservoir, a pump communicated to the drug reservoir, afirst pressure sensor coupled to the pump, an optical source and sensorcircuit coupled to the sending and receiving optical fibers, and amicrocontroller subsystem for controlling the pump and bidirectionallycommunicating with the first pressure sensor and pump and the opticalsource and sensor circuit.
 2. The apparatus of claim 1 where themicrocontroller subsystem for controlling the pump and bidirectionallycommunicating with the first pressure sensor and pump comprises: amicrocontroller; a Bluetooth radio coupled to the microcontroller; anantenna coupled to the Bluetooth radio; a power and analog circuitcoupled to the optical source and sensor circuit, microcontroller andBluetooth radio; and a power source coupled to the pump, to themicrocontroller, to the Bluetooth radio, to the optical source andsensor circuit and to the first pressure sensor,
 3. The apparatus ofclaim 1 further comprising a second pressure sensor coupled to thereservoir and communicated to the microcontroller subsystem, the secondpressure sensor including a selectively operated valve.